A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Author:

Sung Yun Ju1,de las Fuentes Lisa21,Winkler Thomas W3,Chasman Daniel I4,Bentley Amy R5,Kraja Aldi T6,Ntalla Ioanna7,Warren Helen R78,Guo Xiuqing9,Schwander Karen1,Manning Alisa K1011,Brown Michael R12,Aschard Hugues1314,Feitosa Mary F6,Franceschini Nora15,Lu Yingchang16,Cheng Ching-Yu171819,Sim Xueling20,Vojinovic Dina21,Marten Jonathan22,Musani Solomon K23,Kilpeläinen Tuomas O2425,Richard Melissa A26,Aslibekyan Stella27,Bartz Traci M28,Dorajoo Rajkumar29,Li Changwei30,Liu Yongmei31,Rankinen Tuomo32,Smith Albert Vernon3334,Tajuddin Salman M35,Tayo Bamidele O36,Zhao Wei37,Zhou Yanhua38,Matoba Nana39,Sofer Tamar4041,Alver Maris42,Amini Marzyeh43,Boissel Mathilde44,Chai Jin Fang20,Chen Xu45,Divers Jasmin46,Gandin Ilaria47,Gao Chuan48,Giulianini Franco4,Goel Anuj4950,Harris Sarah E5152,Hartwig Fernando P5354,He Meian55,Horimoto Andrea R V R56,Hsu Fang-Chi46,Jackson Anne U57,Kammerer Candace M58,Kasturiratne Anuradhani59,Komulainen Pirjo60,Kühnel Brigitte6162,Leander Karin63,Lee Wen-Jane64,Lin Keng-Hung65,Luan Jian’an66,Lyytikäinen Leo-Pekka6768,McKenzie Colin A69,Nelson Christopher P7071,Noordam Raymond72,Scott Robert A66,Sheu Wayne H H73747576,Stančáková Alena77,Takeuchi Fumihiko78,van der Most Peter J43,Varga Tibor V79,Waken Robert J1,Wang Heming4041,Wang Yajuan80,Ware Erin B8137,Weiss Stefan8283,Wen Wanqing84,Yanek Lisa R85,Zhang Weihua8687,Zhao Jing Hua66,Afaq Saima86,Alfred Tamuno16,Amin Najaf21,Arking Dan E88,Aung Tin171819,Barr R Graham89,Bielak Lawrence F37,Boerwinkle Eric1290,Bottinger Erwin P16,Braund Peter S7071,Brody Jennifer A91,Broeckel Ulrich92,Cade Brian41,Campbell Archie93,Canouil Mickaël44,Chakravarti Aravinda88,Cocca Massimiliano47,Collins Francis S94,Connell John M95,de Mutsert Renée96,de Silva H Janaka97,Dörr Marcus9883,Duan Qing99,Eaton Charles B100,Ehret Georg88101,Evangelou Evangelos86102,Faul Jessica D81,Forouhi Nita G66,Franco Oscar H21,Friedlander Yechiel103,Gao He86,Gigante Bruna63,Gu C Charles1,Gupta Preeti17,Hagenaars Saskia P51104,Harris Tamara B105,He Jiang106107,Heikkinen Sami77108,Heng Chew-Kiat109110,Hofman Albert21,Howard Barbara V111112,Hunt Steven C113114,Irvin Marguerite R115,Jia Yucheng9,Katsuya Tomohiro116117,Kaufman Joel118,Kerrison Nicola D66,Khor Chiea Chuen29119,Koh Woon-Puay12020,Koistinen Heikki A121122123,Kooperberg Charles B124,Krieger Jose E56,Kubo Michiaki125,Kutalik Zoltan126127,Kuusisto Johanna77,Lakka Timo A10860128,Langefeld Carl D46,Langenberg Claudia66,Launer Lenore J105,Lee Joseph H129,Lehne Benjamin86,Levy Daniel130131,Lewis Cora E132,Li Yize1,Lim Sing Hui17,Liu Ching-Ti38,Liu Jianjun2920,Liu Jingmin133,Liu Yeheng9,Loh Marie86134,Lohman Kurt K46,Louie Tin135,Mägi Reedik42,Matsuda Koichi136,Meitinger Thomas137138,Metspalu Andres42,Milani Lili2,Momozawa Yukihide139,Mosley, Jr Thomas H140,Nalls Mike A141,Nasri Ubaydah9,O'Connell Jeff R142143,Ogunniyi Adesola144,Palmas Walter R145,Palmer Nicholette D146,Pankow James S147,Pedersen Nancy L45,Peters Annette61148,Peyser Patricia A37,Polasek Ozren149150151,Porteous David93,Raitakari Olli T152153,Renström Frida79154,Rice Treva K1,Ridker Paul M4,Robino Antonietta155,Robinson Jennifer G156,Rose Lynda M4,Rudan Igor157,Sabanayagam Charumathi1718,Salako Babatunde L144,Sandow Kevin9,Schmidt Carsten O15883,Schreiner Pamela J147,Scott William R86159,Sever Peter160,Sims Mario23,Sitlani Colleen M91,Smith Blair H161,Smith Jennifer A3781,Snieder Harold43,Starr John M51162,Strauch Konstantin163164,Tang Hua165,Taylor Kent D9,Teo Yik Ying2016616729168,Tham Yih Chung17,Uitterlinden André G169,Waldenberger Melanie606165,Wang Lihua6,Wang Ya Xing170,Wei Wen Bin171,Wilson Gregory172,Wojczynski Mary K6,Xiang Yong-Bing173,Yao Jie9,Yuan Jian-Min174175,Zonderman Alan B176,Becker Diane M85,Boehnke Michael56,Bowden Donald W146,Chambers John C8687,Chen Yii-Der Ida9,Weir David R81,de Faire Ulf62,Deary Ian J51104,Esko Tõnu42177,Farrall Martin4950,Forrester Terrence68,Freedman Barry I178,Froguel Philippe44179,Gasparini Paolo47114,Gieger Christian6061180,Horta Bernardo Lessa53,Hung Yi-Jen181,Jonas Jost Bruno171182,Kato Norihiro78,Kooner Jaspal S87159,Laakso Markku77,Lehtimäki Terho6667,Liang Kae-Woei18374184,Magnusson Patrik K E45,Oldehinkel Albertine J185,Pereira Alexandre C55186,Perls Thomas187,Rauramaa Rainer59,Redline Susan41,Rettig Rainer83188,Samani Nilesh J7071,Scott James159,Shu Xiao-Ou84,van der Harst Pim189,Wagenknecht Lynne E190,Wareham Nicholas J65,Watkins Hugh4950,Wickremasinghe Ananda R58,Wu Tangchun69,Kamatani Yoichiro39,Laurie Cathy C135,Bouchard Claude32,Cooper Richard S36,Evans Michele K35,Gudnason Vilmundur3334,Hixson James12,Kardia Sharon L R37,Kritchevsky Stephen B191,Psaty Bruce M192193,van Dam Rob M20194,Arnett Donna K195,Mook-Kanamori Dennis O96196,Fornage Myriam26,Fox Ervin R197,Hayward Caroline22,van Duijn Cornelia M21,Tai E Shyong19420120,Wong Tien Yin171819,Loos Ruth J F16198,Reiner Alex P124,Rotimi Charles N5,Bierut Laura J199,Zhu Xiaofeng80,Cupples L Adrienne38,Province Michael A6,Rotter Jerome I9,Franks Paul W79200201,Rice Kenneth135,Elliott Paul86,Caulfield Mark J78,Gauderman W James202,Munroe Patricia B78,Rao Dabeeru C1,Morrison Alanna C12,

Affiliation:

1. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA

2. Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, USA

3. Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany

4. Preventive Medicine, Brigham and Women’s Hospital, Boston, MA, USA

5. Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

6. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

7. Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

8. NIHR Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, London, UK

9. Division of Genomic Outcomes, Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA

10. Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA

11. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

12. Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA

13. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

14. Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, France

15. Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA

16. Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY, USA

17. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore

18. Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore

19. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

20. Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore

21. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

22. Medical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

23. Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA

24. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

25. Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, NY, USA

26. Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA

27. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

28. Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, WA, USA

29. Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore

30. Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, Athens, GA, USA

31. Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, NC, USA

32. Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA

33. Icelandic Heart Association, Kopavogur, Iceland

34. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

35. Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA

36. Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA

37. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA

38. Biostatistics, Boston University School of Public Health, Boston, MA, USA

39. Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

40. Department of Medicine, Harvard Medical School, Boston, MA, USA

41. Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA

42. Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia

43. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands

44. CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France

45. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, Sweden

46. Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

47. Department of Medical Sciences, University of Trieste, Trieste, Italy

48. Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, USA

49. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK

50. Wellcome Centre for Human Genetics, University of Oxford, Oxford, Oxfordshire, UK

51. Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK

52. Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK

53. Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, RS, Brazil

54. Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK

55. Lab Genetics and Molecular Cardiology, Cardiology, Heart Institute, University of Sao Paulo, Sao Paulo, CA, USA

56. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA

57. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

58. Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka

59. Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland

60. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

61. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

62. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

63. Medical Research, Taichung Veterans General Hospital, Department of Social Work, Tunghai University, Taichung, Taiwan

64. Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan

65. MRC Epidemiology Unit, University of Cambridge, Cambridge, UK

66. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland

67. Department of Clinical Chemistry, Finnish Cardiovascular Research Center—Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

68. Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Jamaica

69. School of Public Health, Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongi Medical College, Huazhong University of Science and Technology, Wuhan, China

70. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

71. NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK

72. Internal Medicine, Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

73. Endocrinology and Metabolism, Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

74. School of Medicine, National Yang-ming University, Taipei, Taiwan

75. School of Medicine, National Defense Medical Center, Taipei, Taiwan

76. Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan

77. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland

78. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan

79. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden

80. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA

81. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA

82. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Ernst Moritz Arndt University Greifswald, Greifswald, Germany

83. DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, Greifswald, Germany

84. Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

85. General Internal Medicine, GeneSTAR Research Program, Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

86. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK

87. Department of Cardiology, Ealing Hospital, Middlesex, UK

88. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

89. Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY, USA

90. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

91. Cardiovascular Health Research Unit, Medicine, University of Washington, Seattle, WA, USA

92. Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

93. Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK

94. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

95. Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK

96. Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

97. Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka

98. Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany

99. Department of Genetics, University of North Carolina, Chapel Hill, USA

100. Department of Family Medicine and Epidemiology, Alpert Medical School of Brown University, Providence, RI, USA

101. Cardiology, Department of Specialties of Medicine, Geneva University Hospital, Geneva, Switzerland

102. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece

103. Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel

104. Psychology, The University of Edinburgh, Edinburgh, UK

105. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

106. Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA

107. Medicine, Tulane University School of Medicine, New Orleans, LA, USA

108. Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Finland

109. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

110. Khoo Teck Puat—National University Children’s Medical Institute, National University Health System, Singapore, Singapore

111. MedStar Health Research Institute, Hyattsville, MD, USA

112. Center for Clinical and Translational Sciences and Department of Medicine, Georgetown–Howard Universities, Washington, DC, USA

113. Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

114. Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar

115. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

116. Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan

117. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Japan

118. Epidemiology, Occupational and Environmental Medicine Program, University of Washington, Seattle, WA, USA

119. Department of Biochemistry, National University of Singapore, Singapore, Singapore

120. Health Services and Systems Research, Duke–NUS Medical School, Singapore, Singapore

121. Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland

122. Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

123. Minerva Foundation Institute for Medical Research, Biomedicum 2U, Helsinki Finland

124. Fred Hutchinson Cancer Research Center, University of Washington School of Public Health, Seattle, WA, USA

125. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

126. Institute of Social Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland

127. Swiss Institute of Bioinformatics, Lausanne, Switzerland

128. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland

129. Sergievsky Center, College of Physicians and Surgeons, Columbia University Mailman School of Public Health, New York, NY, USA

130. NHLBI Framingham Heart Study, Framingham, MA, USA

131. The Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

132. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

133. WHI CCC, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

134. Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore

135. Department of Biostatistics, University of Washington, Seattle, WA, USA

136. Laboratory for Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, Japan

137. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

138. Institute of Human Genetics, Technische Universität München, Munich, Germany

139. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

140. Geriatrics, Medicine, University of Mississippi, Jackson, MS, USA

141. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA

142. Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA

143. Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

144. Department of Medicine, University of Ibadan, Ibadan, Nigeria

145. Internal Medicine, Columbia University, New York, NY, USA

146. Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA

147. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA

148. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Neuherberg, Germany

149. Department of Public Health, Department of Medicine, University of Split, Split, Croatia

150. Psychiatric Hospital ‘Sveti Ivan’, Zagreb, Croatia

151. Gen-info Ltd, Zagreb, Croatia

152. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland

153. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

154. Department of Biobank Research, Umeå University, Umeå, Västerbotten, Sweden

155. Institute for Maternal and Child Health—IRCCS ‘Burlo Garofolo’, Trieste, Italy

156. Department of Epidemiology and Medicine, University of Iowa, Iowa City, IA, USA

157. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK

158. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

159. National Heart and Lung Institute, Imperial College London, London, UK

160. International Centre for Circulatory Health, Imperial College London, London, UK

161. Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

162. Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, UK

163. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

164. Genetic Epidemiology, IBE, Faculty of Medicine, LMU, Munich, Germany

165. Department of Genetics, Stanford University, Stanford, CA, USA

166. Life Sciences Institute, National University of Singapore, Singapore, Singapore

167. NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore

168. Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore

169. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

170. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China

171. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China

172. Jackson Heart Study, School of Public Health, Jackson State University, Jackson, MS, USA

173. State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China

174. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

175. Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, PA, USA

176. Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA

177. Broad Institute of the Massachusetts Institute of Technology and Harvard University, Boston, MA, USA

178. Nephrology, Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

179. Department of Genomics of Common Disease, Imperial College London, London, UK

180. German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany

181. Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taipei, Taiwan

182. Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany

183. Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan

184. Department of Medicine, China Medical University, Taichung, Taiwan

185. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands

186. Department of Genetics, Harvard Medical School, Boston, MA, USA

187. Geriatrics Section, Boston University Medical Center, Boston, MA, USA

188. Institute of Physiology, University of Medicine Greifswald, Greifswald, Germany

189. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands

190. Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

191. Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

192. Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, USA

193. Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA

194. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

195. Dean’s Office, University of Kentucky College of Public Health, Lexington, KY, USA

196. Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands

197. Cardiology, Medicine, University of Mississippi Medical Center, Jackson, MS, USA

198. Icahn School of Medicine at Mount Sinai, The Mindich Child Health and Development Institute, New York, NY, USA

199. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA

200. Harvard T. H. Chan School of Public Health, Department of Nutrition, Harvard University, Boston, MA, USA

201. Department of Public Health & Clinical Medicine, Umeå University, Umeå, Västerbotten, Sweden

202. Biostatistics, Preventive Medicine, University of Southern California, Los Angeles, CA, USA

Abstract

Abstract Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Genetics(clinical),Genetics,Molecular Biology,General Medicine

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